ES2970597T3 - Derivados deuterados de lanifibranor - Google Patents
Derivados deuterados de lanifibranor Download PDFInfo
- Publication number
- ES2970597T3 ES2970597T3 ES19759658T ES19759658T ES2970597T3 ES 2970597 T3 ES2970597 T3 ES 2970597T3 ES 19759658 T ES19759658 T ES 19759658T ES 19759658 T ES19759658 T ES 19759658T ES 2970597 T3 ES2970597 T3 ES 2970597T3
- Authority
- ES
- Spain
- Prior art keywords
- deuterated derivative
- derivative according
- groups
- pharmaceutically acceptable
- mmol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- OQDQIFQRNZIEEJ-UHFFFAOYSA-N 4-[1-(1,3-benzothiazol-6-ylsulfonyl)-5-chloroindol-2-yl]butanoic acid Chemical class C1=C2N=CSC2=CC(S(=O)(=O)N2C3=CC=C(Cl)C=C3C=C2CCCC(=O)O)=C1 OQDQIFQRNZIEEJ-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 230000003176 fibrotic effect Effects 0.000 claims abstract description 11
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 10
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 229910052805 deuterium Inorganic materials 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 206010019708 Hepatic steatosis Diseases 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 3
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 2
- 208000020832 chronic kidney disease Diseases 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 2
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 201000003086 pulmonary systemic sclerosis Diseases 0.000 claims description 2
- 239000003981 vehicle Substances 0.000 claims description 2
- 125000004431 deuterium atom Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 description 29
- 239000000243 solution Substances 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 6
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 229940126032 IVA-337 Drugs 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010048554 Endothelial dysfunction Diseases 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 101150014691 PPARA gene Proteins 0.000 description 2
- 240000002834 Paulownia tomentosa Species 0.000 description 2
- 235000010678 Paulownia tomentosa Nutrition 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- 150000001975 deuterium Chemical group 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000008694 endothelial dysfunction Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- -1 for example Substances 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 208000006575 hypertriglyceridemia Diseases 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
- GOQJMMHTSOQIEI-SQUIKQQTSA-N 1,1,2,2,3,3,4,4-octadeuteriohex-5-yn-1-ol Chemical compound [2H]C([2H])(C#C)C([2H])([2H])C([2H])([2H])C([2H])([2H])O GOQJMMHTSOQIEI-SQUIKQQTSA-N 0.000 description 1
- VPFMEXRVUOPYRG-RUJHVMJGSA-N 2,2,3,3,4,4-hexadeuteriohex-5-ynoic acid Chemical compound [2H]C([2H])(C#C)C([2H])([2H])C([2H])([2H])C(=O)O VPFMEXRVUOPYRG-RUJHVMJGSA-N 0.000 description 1
- FLEJOBRWKBPUOX-UHFFFAOYSA-N 4-chloro-2-iodoaniline Chemical compound NC1=CC=C(Cl)C=C1I FLEJOBRWKBPUOX-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical class [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- MQOBSOSZFYZQOK-UHFFFAOYSA-N fenofibric acid Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C(=O)C1=CC=C(Cl)C=C1 MQOBSOSZFYZQOK-UHFFFAOYSA-N 0.000 description 1
- 229960000701 fenofibric acid Drugs 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- VPFMEXRVUOPYRG-UHFFFAOYSA-N hex-5-ynoic acid Chemical compound OC(=O)CCCC#C VPFMEXRVUOPYRG-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- ARNWQMJQALNBBV-UHFFFAOYSA-N lithium carbide Chemical compound [Li+].[Li+].[C-]#[C-] ARNWQMJQALNBBV-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000012254 magnesium hydroxide Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- ILOZGGRPYUTYCT-UHFFFAOYSA-N n-(4-chloro-2-iodophenyl)-1,3-benzothiazole-6-sulfonamide Chemical compound IC1=CC(Cl)=CC=C1NS(=O)(=O)C1=CC=C(N=CS2)C2=C1 ILOZGGRPYUTYCT-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1857021A FR3084254B1 (fr) | 2018-07-27 | 2018-07-27 | Derives deuteres du lanifibranor |
| PCT/FR2019/051860 WO2020021215A1 (fr) | 2018-07-27 | 2019-07-26 | Derives deuteres du lanifibranor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2970597T3 true ES2970597T3 (es) | 2024-05-29 |
Family
ID=63684156
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES19759658T Active ES2970597T3 (es) | 2018-07-27 | 2019-07-26 | Derivados deuterados de lanifibranor |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20210300913A1 (sr) |
| EP (2) | EP3830085B1 (sr) |
| JP (2) | JP7434278B2 (sr) |
| CN (1) | CN112638911A (sr) |
| DK (1) | DK3830085T3 (sr) |
| ES (1) | ES2970597T3 (sr) |
| FI (1) | FI3830085T3 (sr) |
| FR (1) | FR3084254B1 (sr) |
| HR (1) | HRP20240157T1 (sr) |
| HU (1) | HUE065045T2 (sr) |
| LT (1) | LT3830085T (sr) |
| PL (1) | PL3830085T3 (sr) |
| PT (1) | PT3830085T (sr) |
| RS (1) | RS65095B1 (sr) |
| SI (1) | SI3830085T1 (sr) |
| WO (1) | WO2020021215A1 (sr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102199640B1 (ko) * | 2020-01-06 | 2021-01-07 | 브렉소젠 주식회사 | 라니피브라노르를 포함하는 줄기세포 유래 엑소좀 생성 촉진 및 줄기세포기능 강화용 조성물 |
| EP4000616A1 (en) | 2020-11-17 | 2022-05-25 | Inventiva | Combination therapy for the treatment of a liver disease |
| WO2022143479A1 (zh) * | 2020-12-29 | 2022-07-07 | 广东东阳光药业有限公司 | 一种化合物的固体形式及其制备方法和用途 |
| EP4385990A1 (en) * | 2021-08-12 | 2024-06-19 | Inventiva S.A. | Crystal form of lanifibranor, preparation method therefor, and use thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2890071B1 (fr) * | 2005-08-30 | 2007-11-09 | Fournier Sa Sa Lab | Nouveaux composes de l'indole |
| MX2016016534A (es) | 2014-06-13 | 2017-04-06 | Inventiva | Compuestos ppar para uso en el tratamiento de enfermedades fibroticas. |
| WO2017136375A1 (en) | 2016-02-05 | 2017-08-10 | Concert Pharmaceuticals, Inc. | Deuterated tozadenant |
| WO2018039521A1 (en) | 2016-08-26 | 2018-03-01 | Concert Pharmaceuticals, Inc. | Deuterated cenicriviroc |
| US11504380B2 (en) * | 2019-11-08 | 2022-11-22 | Inventiva | Method of treatment of cirrhosis |
-
2018
- 2018-07-27 FR FR1857021A patent/FR3084254B1/fr active Active
-
2019
- 2019-07-26 PL PL19759658.8T patent/PL3830085T3/pl unknown
- 2019-07-26 WO PCT/FR2019/051860 patent/WO2020021215A1/fr active Application Filing
- 2019-07-26 SI SI201930700T patent/SI3830085T1/sl unknown
- 2019-07-26 US US17/261,938 patent/US20210300913A1/en active Pending
- 2019-07-26 CN CN201980049453.4A patent/CN112638911A/zh active Pending
- 2019-07-26 RS RS20240090A patent/RS65095B1/sr unknown
- 2019-07-26 DK DK19759658.8T patent/DK3830085T3/da active
- 2019-07-26 EP EP19759658.8A patent/EP3830085B1/fr active Active
- 2019-07-26 FI FIEP19759658.8T patent/FI3830085T3/fi active
- 2019-07-26 LT LTEPPCT/FR2019/051860T patent/LT3830085T/lt unknown
- 2019-07-26 JP JP2021504431A patent/JP7434278B2/ja active Active
- 2019-07-26 ES ES19759658T patent/ES2970597T3/es active Active
- 2019-07-26 HR HRP20240157TT patent/HRP20240157T1/hr unknown
- 2019-07-26 PT PT197596588T patent/PT3830085T/pt unknown
- 2019-07-26 HU HUE19759658A patent/HUE065045T2/hu unknown
- 2019-07-26 EP EP23201458.9A patent/EP4331584A1/fr active Pending
-
2024
- 2024-02-07 JP JP2024017170A patent/JP2024036611A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| HRP20240157T1 (hr) | 2024-04-12 |
| EP3830085A1 (fr) | 2021-06-09 |
| DK3830085T3 (da) | 2024-01-22 |
| WO2020021215A1 (fr) | 2020-01-30 |
| PL3830085T3 (pl) | 2024-04-15 |
| EP3830085B1 (fr) | 2023-11-08 |
| JP2021533101A (ja) | 2021-12-02 |
| FI3830085T3 (fi) | 2024-01-17 |
| HUE065045T2 (hu) | 2024-04-28 |
| RS65095B1 (sr) | 2024-02-29 |
| US20210300913A1 (en) | 2021-09-30 |
| SI3830085T1 (sl) | 2024-03-29 |
| EP4331584A1 (fr) | 2024-03-06 |
| PT3830085T (pt) | 2024-01-24 |
| FR3084254B1 (fr) | 2020-10-23 |
| LT3830085T (lt) | 2024-02-12 |
| CN112638911A (zh) | 2021-04-09 |
| JP2024036611A (ja) | 2024-03-15 |
| FR3084254A1 (fr) | 2020-01-31 |
| JP7434278B2 (ja) | 2024-02-20 |
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